Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz

Many genes have been linked to autism. However, it remains unclear what long-term changes in neural circuitry result from disruptions in these genes, and how these circuit changes might contribute to abnormal behaviors. To address these questions, we studied behavior and physiology in mice heterozyg...

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Bibliographic Details
Published in:	eLife Vol. 9
Main Authors:	Cunniff, Margaret M, Markenscoff-Papadimitriou, Eirene, Ostrowski, Julia, Rubenstein, John Lr, Sohal, Vikaas Singh
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 06-11-2020 eLife Sciences Publications, Ltd eLife Sciences Publications Ltd
Subjects:	Animals anxiety Anxiety - genetics Anxiety - physiopathology Autism Autistic Disorder - genetics Autistic Disorder - physiopathology Avoidance Learning Communication Female GABA Genetic aspects Genetic research Heterozygote hippocampus Hippocampus - physiopathology Interneurons Male Mice Neural circuitry Neurons Neuroscience Neurosciences Physiological aspects prefrontal cortex Prefrontal Cortex - physiopathology Pyramidal Cells Theta Rhythm Transposases - genetics Transposases - metabolism anxiety mouse hippocampus neuroscience prefrontal cortex autism theta rhythm
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Summary:	Many genes have been linked to autism. However, it remains unclear what long-term changes in neural circuitry result from disruptions in these genes, and how these circuit changes might contribute to abnormal behaviors. To address these questions, we studied behavior and physiology in mice heterozygous for , a high confidence autism gene. mice exhibit reduced anxiety-related avoidance in the elevated plus maze (EPM). Theta-frequency communication between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) is known to be necessary for normal avoidance in the EPM. We found deficient theta-frequency synchronization between the vHPC and mPFC in vivo. When we examined vHPC-mPFC communication at higher resolution, vHPC input onto prefrontal GABAergic interneurons was specifically disrupted, whereas input onto pyramidal neurons remained intact. These findings illustrate how the loss of a high confidence autism gene can impair long-range communication by causing inhibitory circuit dysfunction within pathways important for specific behaviors.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.54835